Earlier this week, JAMA published phase 2 results from a dose-ranging study (n=632) of Novo Nordisk’s oral semaglutide (the company released topline data in February 2015). Led by Leicester’s Professor Melanie Davies, the study found that 90% of patients in the highest-d0se 40 mg group (n=71) reached a target A1c <7% after 26 weeks. Even among those in the lowest-dose 2.5 mg group (n=70), 44% reached A1c <7% vs. 28% of the placebo group (n=71) and 93% of the group getting semaglutide subcutaneously (n=69). Of all five patient cohorts receiving oral semaglutide, 71% experienced ≥ 5% weight loss, ranging from 5 lbs-15 lbs, though weight loss vs. placebo was only significant at the 10 mg dose and above (p<0.001). All oral semaglutide doses gave significant A1c reductions: Treatment differences vs. placebo were 0.4% for 2.5 mg (p=0.007), 0.9% for 5 mg, 1.2% for 10 mg, 1.4% for 20 mg, and 1.6% for 40 mg (all p<0.001). These results indicate that oral semaglutide can be as efficacious as injectable semaglutide, though significantly larger doses are required (not surprising, given the lower bioavailability of an agent when taken orally vs. subcutaneously). Oral semaglutide is now well into the extensive phase 3 PIONEER program, and in fact, the first of these studies PIONEER 1 (placebo-controlled) is expected to complete in December 2017. Still, we were excited to see more granular detail on the phase 2 data, and it’s always great to see diabetes in JAMA – we see this publication as a reflection of what a scientific breakthrough oral semaglutide would be, not only as the first non-injectable GLP-1 agonist, but as an extremely effective GLP-1 agonist at that. Moreover, this therapy would be a huge win for patient choice, especially for those who struggle to administer injections.
-- by Ann Carracher, Payal Marathe, and Kelly Close